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Updated: Mar 21, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Practical synthesis and cytotoxic evaluation of the pyrazino[1,2-b]-isoquinoline ring system
Eduardo Hernández-Vázquez1, Luis D Miranda
1Departamento de Química Orgánica, Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior S.N., Ciudad Universitaria, Coyoacán, D.F. 04510, México. lmiranda@unam.mx.
Abstract:
A practical three-step protocol for the synthesis of pyrazino[1,2-b]isoquinolines is reported. This approach includes a one-pot parallel cyclization/cyclization parallel process followed by a non-common 6-endo Heck cyclization that transformed previously constructed Ugi adducts into diversely decorated tricyclic systems. Compounds bearing a t-butyl or 2,6-dimethylphenyl substituent showed significant cytotoxic activity. The most active analogue (6p) showed significant activity against HCT-15 and K562 (IC50 = 41.8 ± 3.3 and 57.7 ± 2.1 μM, respectively) with no cytotoxicity against human gingival fibroblasts.
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